Kristine-Gem Estrella, Casey Fulinara, Vicki Luong, Jenny Nguyen, Ryan Odiorne, Maaya Ono,

Adrienne Yoo, Madeline Bui

1. Topic & Journal Information

a. Antidepressants
b. Khan, A., Fahl Mar, K., Gokul, S., & Brown, W. A. (2018). Decreased suicide
rates in recent antidepressant clinical trials. ​Psychopharmacology​, ​235​(5),
1455-1462.
c. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5920087/

2. Search terms you used to obtain the evidence.

a. Antidepressants and suicide rates

3. What were the populations and terms used for statistics used in the article and
define them.
a. Population:
i. Patients over 18 years old who were diagnosed with major depressive
disorder taking 1 of 14 FDA antidepressant medications
b. Sample:
i. Antidepressant and placebo treatment groups, consisting of patients
diagnosed with major depressive disorder who were over 18, between
pre-2000 antidepressant programs and post-2000 programs. The sample
was derived from participants in one of the 14 FDA approved
antidepressant programs (from 1991-2013 including 40,857 patients)

4. List the statistics used and define those as well.

a. Independent Variable: Antidepressant users and placebo users pre-2000 and
post-2000
b. Dependent Variable: Rate of suicide attempts, and Rate of suicide deaths
c. Test: Two-tailed Fisher Exact Test, Confidence Intervals, Z-scores, and P-values
i. Rate of suicide attempts per patient exposure years (PEY) for:
1. Antidepressant-exposed patients
a. Pre-2000: 3975.7 (CI 3417–4598)
b. Post-2000: 645.4 (CI 417.6–952.8)
c. The decrease in suicide attempts, after analysis with
Fisher’s Exact test, was statistically significant (z = 9.74,
p < 0.0001). Since the p-value is less than the
significance level, we reject the null hypothesis. This
suggests that the decrease in suicide attempts was due to
the antidepressants (and not by chance).
2. Placebo-exposed patients
a. Pre-2000: 3538.3 (CI 2289–5222)
b. Post-2000: 522.6.4 (CI 105–1527)
c. The decrease in suicide attempts, after analysis with
Fisher’s Exact test, was statistically significant (z = 3.6,
p < 0.001). Since the p-value is less than the significance
level, we reject the null hypothesis. This suggests that the
 decrease in suicide attempts was due to the placebo (and
not by chance).
ii. Rate of death by suicide per patient exposure years (PEY) for:
1. Antidepressant-exposed patients
a. Pre-2000: 643.5 (CI 450.7–890.0)
b. Post-2000: 25.8 (CI 0.7–143.8)
c. The decrease in death by suicide, after analysis with
Fisher’s Exact test, was statistically significant (z=4.73,
p<0.0001). Since the p-value is less than the significance
level, we reject the null hypothesis. This suggests that the
decrease in death by suicide was due to the
antidepressants (and not by chance).
2. Placebo-exposed patients
a. Pre-2000: 471.1 (CI 128.4-1206.2)
b. Post-2000: 174.2 (CI 4.4-970.5)
c. The decrease in death by suicide, after analysis with
Fisher’s Exact test, was not statistically significant (z=0.93,
p=0.66). Since the p-value is greater than the significance
level, we accept the null hypothesis. This suggests that the
decrease in death by suicide was not due to the placebo.
iii. Drug-placebo differences in suicide attempt rates
1. In pre-2000, the comparison between suicide attempt rates of the
antidepressant group and placebo group was not statistically
significant (​p ​ = 0.60). Because of this, we must accept the null
hypothesis. This suggests that there is no difference in the
treatment methods of the antidepressant group and placebo
group.
2. In post-2000, the comparison between suicide attempt rates of the
antidepressant group and placebo group was not statistically
significant (p = 0.5). Because of this, we must accept the null
hypothesis. This suggests that there is no difference in the
treatment methods of the antidepressant group and placebo
group.
d. Test: Regression Analysis
i. Independent variable: Time (years)
ii. Dependent variable: Rate of death by suicide, and Rate of suicide
attempts
iii. Rate of suicide attempts per 100,000 PEY
1. Antidepressant-exposed patients
a. (Beta = -150.3, R​2​ = 0.33, p = 0.016)
b. Since the p-value is less than the significance level, we
reject the null hypothesis. This means there is a
significance in the decreased rate of suicide attempts over
time in the antidepressant group.
c. The R​2​ value means that the regression model accounts
for 33% of the variance. The closer the R​2​ value is to
100%, the closer the variability is around the regression
line.
 d. From the negative Beta value, this suggests an inverse
relationship between the variables. An increase in number
of years correlates with a decrease in suicide attempts.
2. Placebo-exposed patients
a. (Beta = -196.3, R​2​ = 0.29, p = 0.043)
b. Since the p-value is less than the significance level, we
reject the null hypothesis. This means there is a
significance in the decreased rate of suicide attempts over
time in the placebo group.
c. The R​2​ value means that the regression model accounts
for 29% of the variance. The closer the R​2​ value is to
100%, the closer the variability is around the regression
line.
d. From the negative Beta value, this suggests an inverse
relationship between the variables. An increase in number
of years correlates with a decrease in suicide attempts.
iv. Rate of death by suicide per 100,000 PEY
1. Antidepressant-exposed patients
a. (Beta = -34.0, R​2​ = 0.49, p <0.001)
b. Since the p-value is less than the significance level, we
reject the null hypothesis. This means there is a
significance in the decreased rate of death by suicide over
time in the antidepressant group.
c. The R​2​ value means that the regression model accounts
for 49% of the variance. The closer the R​2​ value is to
100%, the closer the variability is around the regression
line.
d. From the negative Beta value, this suggests an inverse
relationship between the variables. An increase in number
of years correlates with a decrease in death by suicide.
2. Placebo-exposed patients
a. (p = 0.22)
b. Since the p-value is greater than the significance level, we
accept the null hypothesis. This means there is no
significance in the decreased rate of death by suicide over
time in the placebo group.
v. Test: Independent T-Test
1. Age
a. Pre-2000: Mean 45.2 (± 3.0)
b. Post-2000: Mean: 42.9 (± 1.7)
c. t = 1.63, p = 0.142. There is no significant change of
patient age; p-value is greater than significance level.
2. Female ratio
a. Pre-2000: 59.7% female (± 13.7)
b. Post-2000: 63.0% female (± 3.8)
c. t= -0.56, p =0.60. There is no significant change in patient
sex; p-value is greater than significance level.
 e. Null Hypothesis: In patients using antidepressants, there is no change in the
number of deaths by suicide and suicide attempts between pre-2000 and
post-2000.
f. Alternative Hypothesis: In patients using antidepressants, the number of deaths
by suicide and suicide attempts changed between pre-2000 and post-2000.

5. If able, give some evaluation of the statistics used and the results.
a. “The decrease in suicide and suicide attempt rates observed in the
antidepressant treatment group were also seen in the placebo group, indicating
that medication treatment effects are not likely responsible for the overall
observed decline”
b. “Overall, these data support our hypothesis that patients in investigational
antidepressant programs after 2000 had a lowered rate of death by suicide and
suicide attempts.”
c. Suicide attempts and suicide rates have decreased post-2000 compared to
pre-2000 during antidepressant trials. However, this reduction does not seem to
be due to changes in demographics, and likewise, statistical analysis does not
indicate that it’s due to effects from the medication (antidepressants or placebo).
This trend could be explained by more stringent screening processes that were
employed while forming the sample groups.

6. Identify clinical question that addresses diagnosis, prognosis, risk, or treatment.

a. Clinical question addressing prognosis: “What are the effects of antidepressants
on prevalence of death by suicide and suicide attempts pre-2000 and post-2000
clinical trials?”
b. More general clinical question addressing prognosis: “Are antidepressants
effective in preventing death by suicide and suicide attempts?”